No abstract

Human enterovirus 71 (EV-A71) infections cause a wide array of diseases ranging from diarrhoea and rashes to hand-foot-and-mouth disease and, in rare cases, severe neurological disorders. No specific antiviral drug therapy is currently available. Extracts from seventy-five Chinese medicinal plants selected for antiviral activity based on the Chinese pharmacopeia and advice from traditional Chinese medicine clinicians were tested for activity against EV-A71. The aqueous extract of the rhizome of Cimicifuga heracleifolia (Sheng Ma) and Arnebia euchroma (Zi Cao) showed potent antiviral activity. The active fractions were isolated by bioassay-guided purification, and identified by a combination of high-resolution mass spectrometry and NMR. Fukinolic acid and cimicifugic acid A and J, were identified as active anti-EV-A71 compounds for Cimicifuga heracleifolia, whereas for Arnebia euchroma, two caffeic acid derivatives were tentatively deduced. Commercially available fukinolic acid analogues like L-chicoric acid and D-chicoric also showed in vitro micromolar activity against EV-A71 lab-strain and clinical isolates.

Warburgia ugandensis Sprague subspecies ugandensis is a plant widely distributed in Eastern, Central and Southern Africa. In humans, it is used to treat respiratory infections, tooth aches, malaria, skin infections, venereal diseases, diarrhea, fevers and aches. Aim of the studyThis study aims to identify the bioactive compounds against clinically important biofilm-forming strains of Candida and staphylococci that are responsible for tissue and implanted device-related infections. MethodsUsing a bioassay-guided fractionation approach, hexane -, ethanol -, acetone -and water extracts from the leaves of W. ugandensis, their subsequent fractions and isolated compounds were tested against both developing and preformed 24h-biofilms of Candida albicans SC5314, Candida glabrata BG2 Candida glabrata ATCC 2001, Staphylococcus epidermidis 1457 and Staphylococcus aureus USA 300 using microtiter susceptibility tests. Planktonic cells were also tested in parallel for comparison purposes. Confocal scanning laser microscopy was also used to visualize effects of isolated compounds on biofilm formation. ResultsWarburganal, polygodial and alpha-linolenic acid (ALA) were the major bioactive compounds isolated from the acetone extract of W. ugandensis. For both warburganal and polygodial, the biofilm inhibitory concentration that inhibits 50% of C. albicans developing biofilms (BIC 50 ) was 4.5±1 and 10.8±5 μg/mL respectively. Against S. aureus developing biofilms, this value was 37.9±8 μg/mL and 25 μg/mL with warburganal and ALA respectively. Eradication of preformed h biofilms was also observed. Interestingly, synergy between the sesquiterpenoids and azoles against developing C. albicans biofilms resulted in an approximately ten-fold decrease of the effective concentration required to completely inhibit growth of the biofilms by individual compounds. The hydroxyl group in position C-9 in warburganal was identified as essential for activity against staphylococcal biofilms. We also identified additional promising bioactive sesquiterpenoids; drimenol and drimendiol from the structure-activity relationship (SAR) studies. ConclusionsALA and four sesquiterpenoids: polygodial, warburganal, drimenol and drimendiol, have shown biofilm-inhibitory activity that has not been reported before and is worth following up. These compounds are potential drug candidates to manage biofilm-based infections, possibly in combination with azoles.

Holigarna caustica (Dennst.) Oken is used by the tribes of Northeast India for the treatment of intestinal problems. Therefore, the present study was undertaken to investigate the active principles of this plant responsible for its anthelmintic activity, using bioassay-guided fractionation. An ethanol extract of H. caustica fruit was fractionated on a silica gel column, followed by HPLC, while nematicidal activity was followed throughout on Caenorhabditis (C.) elegans as a model organism. Our study constitutes the first nematicidal report for this plant. Bioassay-guided purification led to the isolation of one compound (IC50 = 0.4 µM) as the only active constituent in the most active fraction. The compound was identified as linoleic acid based on spectroscopic data (1H and 13C NMR and ESI-MS). No cytotoxicity was observed in the crude extract or in linoleic acid (up to 356 µM). The results support the use of H. caustica for the treatment of intestinal problems by traditional healers in India.

No abstract

Many mosquito species take bloodmeals predominantly from either birds or mammals. Other mosquito species are less host-specific and feed readily on both. Furthermore, some species tend to alter their feeding patterns over the course of the year; early in the mosquito season such species may feed primarily on a particular host type, and subsequently take an increasingly larger proportion of their bloodmeals from an alternative host type as the season progresses. We have examined the feeding patterns of the three mosquito species found in Bernalillo County, NM: Culex quinquefasciatus (Say), Culex tarsalis (Coquillett), and Aedes vexans (Meigen). Specifically, we seek to determine if any of these species displays a seasonal shift in terms of its host utilization pattern. Our analysis focuses on these three species because they are all considered to be competent vectors for the West Nile virus (WNV). Our current data for Cx. quinquefasciatus suggest that unlike elsewhere in its range, this species increases its proportion of avian bloodmeals as the season progresses. Alternatively, Ae. vexans feeds primarily on mammals, whereas Cx. tarsalis appears to feed on both mammals and birds throughout the mosquito season. A more complete understanding of the feeding habits of these three mosquito species may help to clarify the transmission dynamics of WNV in Bernalillo County.

a b s t r a c tDifferent approaches for the synthesis of 1-benzyloxypyrazin-2(1H)-one derivatives from simple amino acids have been investigated. A library of 33 precursors for the preparation of N-hydroxy pyrazinones was obtained in moderate to good yields.

Polyether alkyl urea derivatives were synthesized, and their properties as gelators in solvents commonly used in cosmetic formulations such as Labrafac cc, isopropyl myristate, and isododecane were investigated. A solvent-free larger-scale (up to 70 g) hydrophobic functionalization of the polyetheramines was carried out by one-step reaction with alkyl or aryl-containing isocyanates, which resulted in the formation of urea-functionalized polyethers. Systematic structural studies were conducted by varying the nature and molecular weight of the polyether backbone and the length of the linker and the side chain. The gels obtained have an appearance varying from opaque to transparent, and their properties were characterized by rheological measurements and small-angle X-ray scattering (SAXS) studies. Rheological analysis indicated the dependence of the gel properties on the hydrophobicity of the alkyl end groups and the type of polyether backbone. SAXS measurements revealed a topological description of the network structures of these materials wherein the gels obtained in Labrafac cc form defined structures from the fiber bundles, while those in isopropyl myristate produce clusters. The results obtained in this study offer potential applications in perfume and cosmetic formulations.